(a) Field of the Invention
This invention relates to novel tetrahydrocarbazole derivatives, to a process and to intermediates for preparing the derivatives, to methods for using the derivatives and to compositions and therapeutically acceptable salts of the derivatives.
More specifically, the present invention relates to novel 1,2,3,4-tetrahydrocarbazole and 1,2,3,4-tetrahydrocyclopent[b]indole derivatives having a hydroxyalkanamine group. These derivatives are useful as diuretic agents in a mammal at dosages which do not elicit undesirable side effects. The combination of these attributes render the 1-hydroxyalkanamine tetrahydrocarbazole derivatives of this invention therapeutically useful.
The 1-hydroxyalkanamine tetrahydrocarbazole derivatives of this invention belong to a special class of diuretic agents which antagonize the renal effects of mineralocorticoids. As a result, these compounds are useful in treating hyperaldosteronism by increasing urine volume and sodium and chloride excretion without affecting potassium excretion. Also, these compounds find utility in the treatment of edema and hypertension.
(b) Description of the Prior Art
A number of reports dealing with tetrahydrocarbazole derivatives are available. For instance, a number of these derivatives are reported by C. A. Demerson et al., in U.S. Pat. No. 3,843,681, issued Oct. 22, 1974; C. A. Demerson et al., in U.S. Pat. No. 3,880,853, issued Apr. 29, 1975; Dostert et al., U.S. Pat. No. 3,859,304, issued Jan. 7, 1975 and A. A. Asselin et al., U.S. Pat. No. 4,128,560, issued Dec. 5, 1978.
The compounds of the present invention are distinguished from the compounds of the above prior art by the nature of the substituents on the tetrahydrocarbazole nucleus and by their pharmacologic properties. More specifically, the novel compounds of this invention are distinguished from the prior art compounds by having a hydroxyalkanamine group. In addition, the novel 1-hydroxyalkanamine tetracarbazole derivatives of this invention possess useful diuretic activity in mammals, a pharmacologic activity not previously reported for tetracarbazole derivatives.
Asselin et al., application Ser. No. 904,081, filed May 8, 1978, now Pat. No. 4,179,503, shows 1,3,4,9-tetrahydropyrano[3,4-b]indole and 1,3,4,9-tetrahydrothiopyrano[3,4-b]-indole derivatives having a hydroxyalkanamine and a lower alkyl group at position 1. The compounds of the present invention are distinguished therefrom in having a different ring structure.